US3351049A - Therapeutic metal seed containing within a radioactive isotope disposed on a carrier and method of manufacture - Google Patents

Therapeutic metal seed containing within a radioactive isotope disposed on a carrier and method of manufacture Download PDF

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US3351049A
US3351049A US447251A US44725165A US3351049A US 3351049 A US3351049 A US 3351049A US 447251 A US447251 A US 447251A US 44725165 A US44725165 A US 44725165A US 3351049 A US3351049 A US 3351049A
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seed
radioactive
container
ray
soft
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US447251A
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Donald C Lawrence
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HAZLETON NUCLEAR SCIENCE CORP
HAZLETON-NUCLEAR SCIENCE Corp
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HAZLETON NUCLEAR SCIENCE CORP
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00Radiation therapy
    • A61N5/10X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
    • A61N5/1001X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy using radiation sources introduced into or applied onto the body; brachytherapy
    • A61N5/1027Interstitial radiation therapy
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/12Preparations containing radioactive substances for use in therapy or testing in vivo characterised by a special physical form, e.g. emulsion, microcapsules, liposomes, characterized by a special physical form, e.g. emulsions, dispersions, microcapsules
    • A61K51/1282Devices used in vivo and carrying the radioactive therapeutic or diagnostic agent, therapeutic or in vivo diagnostic kits, stents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M31/00Devices for introducing or retaining media, e.g. remedies, in cavities of the body
    • GPHYSICS
    • G21NUCLEAR PHYSICS; NUCLEAR ENGINEERING
    • G21FPROTECTION AGAINST X-RADIATION, GAMMA RADIATION, CORPUSCULAR RADIATION OR PARTICLE BOMBARDMENT; TREATING RADIOACTIVELY CONTAMINATED MATERIAL; DECONTAMINATION ARRANGEMENTS THEREFOR
    • G21F5/00Transportable or portable shielded containers
    • G21F5/015Transportable or portable shielded containers for storing radioactive sources, e.g. source carriers for irradiation units; Radioisotope containers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00Radiation therapy
    • A61N5/10X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
    • A61N5/1001X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy using radiation sources introduced into or applied onto the body; brachytherapy
    • A61N2005/1019Sources therefor
    • A61N2005/1024Seeds

Definitions

  • This invention relates to therapeuti radiology. More particularly, it relates to a radioactive X-ray emitting source usually referred to as a seed and a method of manufacture therefor.
  • Radiation therapy refers to the treatment of diseases especially the treatment of tumors including malignant tumors, such as cancer, with radiation.
  • malignant tumors such as cancer
  • radiation therapy it is desired to destroy the malignant tissue without causing excessive radiation damage to nearby healthy and possibly vital tissues which, because of their proximity, are likely to receive considerable irradiation.
  • Radioactive substances in the form of seeds which are implanted at the region to be irradiated.
  • Radioactive materials which have been used to make such seeds have included radon, radium, and radiogold. Seeds constructed of these materials have been made by methods developed over the last several decades and have been used quite beneficially in therapy. However, the seeds heretofore employed have had several disadvantages which have reduced their use.
  • the high energy penetrating power of the characteristic radiations of these materials of prior use makes it very diflicult to adequately shield the administering personnel from these emitted radiations.
  • the surgeon who makes the implant of the seed can receive a considerable dosage in his hands or other parts of his body. While under treatment, the patient must be segregated and shielded from others which causes additional expense and inconvenience.
  • Another disadvantage results from the irradiation of the patients healthy tissues outside of the diseased area being treated due to the excessive penetrating power of the radiation produced by the hitherto employed radiation source materials.
  • Another object of the invention is to provide a source and method of manufacture of the above character in which a therapeutic dosage of the desired radioactive material is confined in an encapsulating medium which prevents any migration of leakage from such encapsulation.
  • Another object of the invention is to provide a improved source and method of manufacture therefor of the above character which will last sufliciently Ion-g to provide a desired amount of radiation and yet not so long as to require removal by surgery after it has performed its function.
  • Another object of the invention is to provide a source and method of manufacture therefor of the above character in which a therapeutic amount of the appropriate radioactive isotope is encapsulated.
  • Another object of the invention is to provide a source and method of manufacture therefor of the above character in which the encapsulating medium is nontoxic, corrosion resistant and compatible with biological fluids so that the seed can be left indefinitely in place.
  • Another object of the invention is to provide a source and method of manufacture therefor of the above character in which the encapsulating medium represents a uniform shadowing effect with respect to the radiations emanated therefrom so that the value of the radiation pattern about the seed is substantially uniform.
  • Another object of the invention is to provide a source and method of manufacture therefor of the above character in which the radioactive material is uniformly distributed throughout the seed interior so as to prevent localization of the radioactive material and consequent undesirable point source effects.
  • Another object of the invention is to provide a source and method of manufacture therefor of the above character which can be detected by standard X-ray techniques so that the position of each source can be plotted and the dosage distribution computed.
  • Another object of the invention is to provide a source and method of manufacture therefor of the above character which retains the substantially uniform radiation pattern thereabout.
  • FIGURE 1 shows a greatly enlarged view of a radioactive source made in accordance with the present invention with portions thereof partially broken away.
  • FIGURE 2 is a greatly enlarged view of a radioactive source of another embodiment of the invention with the portions thereof partially broken away.
  • FIGURE 3 is an enlarged view of another embodiment of the invention and showing, in particular, ball means for making the source X-ray detectable.
  • FIGURE 4 shows a greatly enlarged view of yet another radioactive source made in accordance with the present invention and showing wire means for making the radioactive source X-ray detectable.
  • This invention is predicated upon the observation that there is a class of radioactive isotopes which characteristically emit a radiation principally limited to low energy X-rays and which have half-lives which are appropriate for obtaining optimum benefits of radiation therapy with seeds while avoiding disadvantages of prior radiation source materials.
  • These isotopes are unique in that their half-lives are sutficiently short that they decay predictably to a negligible output level and therefore can be left permanently and indefinitely implanted within the biological specimen treated.
  • the radiation energy output intensity and half-lives are sufficiently long to deliver a radiation exposure over an ideal period of time for the optimal therapeutic effect.
  • the radiation exposure lasts long enough to provide the desired amount of irradiation and yet not so long as to require that the seed be removed by surgery after it has performed its function.
  • the characteristic radiations of such isotopes are essentially free of alpha and beta emissions, greater than 95% of the radiation being low energy X-rays of energy less than 100 thousand electron volts (hereinafter kev.).
  • the tissue can be effectively treated while at the same time such radiations can be easily and completely shielded by a relatively thin layer of dense, high-atomic-number material.
  • the preferred isotopes for use with the invention have radiation characteristics which satisfy the following criteria: a half-life in the range of about 5 to 100 days and preferably about 8 to 80 days.
  • the preferred isotopes are selected with a radiation energy in the soft-X-ray region from about 20 to 100 kev.
  • the radiation energy has a value of about 30 kev.
  • Soft X-rays of the above limited energies are easily shielded by thin layers of gold, silver, etc.,"and yet have a reasonable range in soft tissue, the half-value layer being about 2 centimeters. Radioisotopes with half-lives of less than 5 days are generally too short to permit practical processing of the radioisotopes for fabrication and use. Radioisotopes having halflives longer than 100 days emit significant radiation for years and therefore would necessitate removal.
  • isotopes examples include the monoenergetic X-ray emitting isotopes iodine-125 and cesium- 131. These isotopes have characteristic radiations chiefly consisting of approximately 30 kev. energy X-rays and they also possess half-lives of about 60 and 10 days, respectively.
  • Another isotope example is the isotope palladium-103 having characteristic radiation of about 20 kev. energy and a half-life of about 17 days.
  • radioactive iodine has not heretofore been usable for localized treatment of diseased tissue except in the treatment of thyroid tissue, since when iodine is introduced into the body, it tends to concentrate almost entirely in that gland. Consequently, treatment of tissues in other parts of the body with radioactive iodine has not been possible.
  • this isotope has not been used due to the 'fact that it typically distributes uniformly throughout the body and is not long retained in effective concentrations at the location to be treated.
  • the radioactive seed device of the invention is characterized in that the selected radioisotope is encapsulated in such a manner that it cannot migrate through the encapsulating medium, thereby preventing escape and distribution of the radioisotope throughout the body and possible assimilation and concentration of it in healthy tissues, while, at the same time, permitting the soft X-rays to pass through the capsule wall.
  • the present invention is able to utilize to advantage the ideal properties of this particular class of radioactive isotopes (i.e.
  • the seed need not be surgically removed from the body but may be left in place indefinitely.
  • the seed 10 comprises a therapeutic amount of a selected X-ray emanating radioisotope 11 appropriately distributed on a carrier body 12 disposed interiorly of a tubular container 13.
  • the container is sealed at its ends 14 and 15 and serves to isolate the radioisotope from physical or chemical interchange between body fluids and the interior of the container while at the same time permitting the radiation to pass through the walls of the container.
  • the selected radioisotope is preferably uniformly distributed along the carrier body 12 to avoid having a point source and to maintain a permanent distribution of the radioactive isotope in a fixed bed throughout the extent of the seed. This configuration assures the optimum dose distribution and the best therapeutic effect.
  • the distribution of the radioisotope can take the form of a uniform laminar distribution along the carrier body and within the capsule.
  • the container 13 is preferably designed for implantation as by perforate penetration or injection, e.g., by hypodermic needle or similar device especially designed therefor.
  • the container 13 is preferably constructed in an elongated outside shape, having a relatively narrow outside diameter of from about .5 to 1 millimeter, and about 5 millimeters in length.
  • the interior of the container 13 includes a cavity for receiving the carrier body 12, as hereinafter described.
  • the outside diameter of the seed is constructed about 0.75 millimeter and is thus small enough to pass through a hypodermic needle.
  • the seed is constructed approximately 4 mm. long so that it will have a minimal movement in tissue and will not migrate from the area to be treated.
  • the capsule material should be selected from low-atomic-number materials, preferably of atomic number lying in the range of 4-28. The material must be corrosion resistant, compatible with body tissue and nontoxic, or be provided with a coating possessing these properties. By utilizing low-atomic-number material, absorption is held to a satisfactory low level, consistent with a wall thickness sufficient for structural integrity.
  • the container 13 is constructed of the low atomic numbered metal such as stainless steel alloy or titanium.
  • the stainless steel alloy has been found to have several advantages in that it can be sealed to avoid any migration of contents and it is corrosion resistant, compatible, an nontoxic in use and has a sufficiently low atomic number so that it does not unduly absorb the soft X-rays.
  • the attenuation of stainless steel is about 15% per thousandths of an inch for which additional radioisotope is added to compensate for absorption losses in the container walls.
  • the optimum thickness of stainless steel Wall is in the range of .0005- .003 of an inch. A preferred thickness is about .002 of an inch which represents the best compromise between strength and attenuation losses.
  • Titanium having a lower atomic number and higher strength to weight ratio than stainless steel, is exceptionally corrosion resistant and is equally satisfactory from the standpoint of compatibility and nontoxicity in the intended use. Titanium should be selected as a rather pure alloy to assure good working characteristics.
  • the wall thickness of the titanium may vary from .001 of an inch to .005 of an inch, the attenuation being about 5% per thousandths of an inch. An optimum value of wall thickness is approximately .002 of an inch. Titanium has several advantages over stainless steel as a container material. It has high strength to weight ratio, about one-third the attenuation, and it can be sealed by various simple techniques, such as cold compression bonding.
  • a metal having a relatively high wall thickness of the container would have to be so small for a source containing a given amount of radioisotope and having the same strength, that the physical strength of the source would be impaired. Otherwise, the amount of radioisotope would have to be increased so much that cost considerations would prevent its use.
  • High atomic numbered materials may be useful, however, as plating over a toxic metal of a low atomic number, without absorbing too great an amount of the radiation. Therefore, to use a low atomic numbered material, such asberyllium, requires that it be supplied with an outer coating of nontoxic, corrosion resistant material such as gold.
  • a container constructed of beryllium can have a wall thickness as high as .035 inch.
  • the carrier body 12 is provided for collecting, concentrating and supporting the radioisotope and for maintaining it in an appropriately distributed form throughout the container.
  • the carrier body 12 may be formed in a shape generally conforming to that of the interior of the container in which it is to be disposed so that it will not shift in the container.
  • the carrier body 12 when disposed in a cylindrical container, the carrier body 12 extends in a cylindrical form substantially throughout the interior thereof and has a diameter approximating that of the inside diameter of the container 13.
  • the carrier body 12 is constructed of any suitable material which will chemically or physically capture the selected radioisotope to thereby maintain a uniform distribution of the isotope in a fixed bed.
  • Such material is preferably selected from the materials composed of elements of low-atomic-number so as to minimize internal absorption of the X-ray radiations.
  • the body 12 of selected carrier material is impregnated with the appropriate radioactive isotope at a level suflicient to make up the therapeutic dosage, making allowance for absorption by the encapsulating material.
  • the carrier body 12 is impregnated, it is placed within the container 11 which is then sealed.
  • the seal of the container must prevent migration of the radioisotope and must not possess undesirable radiation shielding properties which may result from the geometrical configuration of the end. Such undesirable properties causes a shadow effect in the radiation pattern at the region near the ends of the tube.
  • the ends 14 and 15 of the container are closed and sealed.
  • this can be accomplished conveniently by closing over the end of the container as by swaging it shut with a swage block having an interior configuration corresponding to the desired exterior configuration at the end of the container.
  • the end of the container is fused, as by welding, into a uniform shell.
  • the container is made into a one-piece unitary structure having a substantially uniform wall thickness.
  • the particular method of formation of the end seal differs somewhat depending upon the par: ticular material chosen for the container.
  • the end is mechanically deformed, as by swaging or spinning, to generally close .over the end and then is fused by welding. It is also possible for the ends to be formed by intermetallically joining the walls under pressure or by ultrasonic welding.
  • ends have been fused by capacitor discharge arc welding. This may tend to thicken the end wall of the container in which case the fused portion is easily trimmed down so that the finished container has a uniform wall thickness throughout.
  • Titanium metal which should be selected from a relatively pure alloy having good formability and heat treatability characteristics, is sealed by-spinning the end of the tube down to a point as by turning and spinning by well known techniques. After this, the end may be fused by welding to obtain the end wall of uniform thickness.
  • the radioactive isotope is distributed uniformly along the length of an elongate carrier body member 21 which is placed inside an aluminum alloy tube 22 (such as that designated by 3003) which is closed over and sealed at its ends 23.
  • the aluminum tubing is sealed in an inert overcoating or container of plastic, ceramic, or precious metal, to prevent reaction of the aluminum with the body fluids over long periods of time.
  • Organic plastic material such as nylon, silicone rubber, polyester resin, or fluorinated hydrocarbons may be used to form the container 24.
  • the fluorinated hydrocarbon Teflon FEP has been found to be a very suitable material in that it is exceptionally nonreactive and nontoxic in biological tissues and is available as a heat shrinkable and heat sealable tubing of small diameter.
  • the seed as shown in FIGURE 2, is very easily manufactured.
  • a short length of aluminum tubing is cut off and sealed at one end.
  • the carrier body 21 containing the active materials is disposed in the aluminum tubing which is then formed to close upon itself at the open and sealed end.
  • the sealed tubing 22 is then placed inside .a plastic tubing which is cut and sealed at its ends by heating.
  • heat shrinkable plastics the application of heat, as by an air blast torch, causes not only the ends to seal but the Whole shell to shrink about the tubing 22 to make a very neat, smooth source.
  • the embodiment as shown in FIGURE 2 is suitable for any of the isotopes contemplated and, in particular, for the isotope iodine-125.
  • the seal provided at the ends of the metal tubing 22 effectively acts to prevent any migration of the iodide out of the capsule.
  • any cold spots insufliciently'irradiated areas
  • they can then be treated by external radiation therapy or other means to greatly improve the chances for destroying the malignancy completely.
  • the necessary low atomic number materials of the seeds are not normally visible on an X-ray.
  • FIG. URE 3 there is provided a small ball 26 which is positioned midway in the seed, the carrier body within the seed being formed into portions 27a and b.
  • the ball 26 is constructed of a dense, high-atomic-number material, such as gold, tungsten, etc.
  • the ball 26 is constructed to have a diameter of approximately .002 to .020 of an inch in order to render an image in the X-ray.
  • the carrier bodies 27a and b and ball 26 are housed in a container 28 in the manner heretofore described in connection with the embodiment of FIGURE 1.
  • FIGURE 4 there is shown another embodiment utilizing a wire 31 located centrally at the axis of symmetry of the carrier body 32 which is disposed in the low atomic numbered material container 33 in the manner previously described with respect to the embodiment of FIGURE 1.
  • the wire is made of a high atomic number dense material, such as gold, tungsten, etc., and is about .002 to .005 inch in diameter.
  • Tungsten is a particularly suitable material in that its absorption for X-rays of the energy commonly employed to take X-ray photographs is somewhat higher than its absorption of the lower energy X-rays which are emitted by the radioactive isotopes utilized in this invention.
  • the location of the high atomic number material should be such as to permit as uniform a radiation pattern as possible from the seed.
  • the ball 26 of FIGURE 3 presents some shielding effects about the midsection of the seed, but this shielding appears to be tolerably small.
  • IODINE125 A nylon filament 82 mm. long was placed in an aqueous 'bath of 25 millicuries of carrier free I-125. The pH was adjusted to a pH higher than seven by the addition of NaOH, and suflicient NaHSO added to assure that essentially all the iodine-125 was in the iodide oxidation state.
  • the pH was then adjusted to acidic (about pH 3) by the addition of sulfuric acid, sodium nitrite (NaNO was then added to oxidize the iodide to free iodine (I Due to the relative insolubility of free iodine in water and the afiinity of the nylon organic for free iodine, substantially all of the free iodine selectively entered the nylon filament and was removed from the bath.
  • the filament was then taken from the bath and dried and cut into lengths of about 3 /2 mm.
  • the filament lengths were mounted into stainless steel tubular containers. Each container was about 4 mm. long and had an outside diameter of approximately .025 inch and was previously sealed at one end. The containers were then sealed at the other end by being shaped and fused shut in the manner previously described.
  • Cesium-131 is separated from the parent barium-131 (which may be produced by neutron irradiation of barium-l30) by selective ion exchange in a column containing [ammonium phosphomolybdate (NH 3 [PMo O (AMP) together with asbestos. Afterwards, the purified cesium- 131 is eluted from the AMP and formed into a bath.
  • barium-131 which may be produced by neutron irradiation of barium-l30
  • AMP ammonium phosphomolybdate
  • Suitable carrier bodies comprise extruded rods, formed of cellulose acetate binder, acetone and AMP. These rods are used as carrier bodies for absorbing and carrying the predetermined dosage level of cesium-131 available in the bath.
  • the bath is made at least slightly acidic and the rods are placed therein.
  • the preferential affinity of the AMP in the rod absorbs the cesium out of the bath and after which the rods are removed from the bath, dried and sealed with a plastic sealer, such as acrylic plastic, for easier handling.
  • the rods are then encapsulated in suitable containers, such as stainless steel or plastic covered aluminum containers previously described.
  • PALLADIUM-103 Palladium strongly self-absorbs soft X-rays.
  • a thin layer of the radioactive palladium-103 (preferably carrier free) is plated on a plastic rod (nylon) approximately 3 /2 mm. long to a strength of a few millicuries.
  • the rod is then encapsulated in plastic covered (nylon or fluorinated hydrocarbon) aluminum containers as in FIGURE 2. Since the characteristic radiation of the palladium-103 is about 20 kev., an appreciable amount would be absorbed and attenuated by use of material such as stainless steel, rendering the latter economically impractical as an encapsulating material for this radioisotope.
  • the effective atomic number of the materials of construction should be as low as practicable (preferably between 4 and 13).
  • an aluminum-plastic capsule is quite suitable.
  • radioactive materials which are especially suited to this application, there are others such as xenon-133 and ytterbium-169 which can be used if proper precautions are taken.
  • the latter isotopes emit only about 50% characteristic X-ray radiations of the desired type, the remainder being essentially higher energy gamma and beta rays which would require additional shielding.
  • a radioactive seed for use in radiation therapy of tissue comprising a sealed container having an elongate cavity therein and constructed with walls of substantially uniform thickness, a therapeutic amount of soft X-ray emanating radioisotope disposed within said cavity, said soft X-ray emanating isotope having a characteristic radiation substantially all of which lies between about 20 kev. and kev.
  • said isotope having a half-life from about 8 to 100 days, and means disposed within said cavity for maintaining said radioisotope in a substantially uniform distribution along the length of said cavity, said last named means being made of a material selected to have low absorption for soft X-rays to thereby minimize internal absorption, said container including walls being made of a metal selected to have a relatively low atomic number to thereby minimize the absorption of soft X-rays while completely containing the isotope, said metal being further selected to be nontoxic and nonsoluble in the tissue being treated.
  • a seed for use in radiation therapy of tissue comprising a sealed container having an elongate cavity therein and constructed with walls of substantially uniform thickness, a carrier body means having dimensions for fitting within said cavity and a therapeutic amount of soft X-ray emanating radioisotope uniformly distributed along said carrier body means, said radioisotope being selected from the group consisting of iodine-125, cesium-131, and palladium-103, said carrier body means serving to physically retain the radioisotope in such uniform distribution, said carrier body means being further selected to have a low absorption for soft X-rays to thereby minimize internal absorption, said container being made of a metal having a relatively low atomic number to minimize absorption of soft X-rays while completely containing the isotope, said metal being selected to be nontoxic and nonsoluble in the tissue to be treated.
  • a radioactive seed as in claim 2 in which said radioisotope is palladium-103, and in which the carrier body means is a plastic rod, the palladium-103 being plated on the plastic rod.
  • a radioactive seed as in claim 1 in which the length of the seed is about four mm. and the lateral crosssectional dimension is small enough to permit injection through a hypodermic needle.
  • a seed as in claim 1 in which said metal selected to have a relatively low atomic number is stainless steel having a thickness from about .0005 inch to .003 inch.
  • a seed as in claim 1 in which said metal selected to have a relatively low atomic number is titanium having a thickness from about .001 inch to .005 inch.
  • a radioactive seed for use in radiation therapy comprising a stainless steel tube having its ends fused, and carrier body means formed of an organic polymer containing the radioactive iodine isotope I dispersed therealong, said carrier body being disposed axially within said stainless steel tube.
  • a radioactive seed for use in radiation therapy comprising a stainless steel tube of relatively narrow diameter having its ends fused, a nylon filament containing the radioactive iodine isotope I dispersed therealong, said nylon filament being disposed axially within said stainless steel tube.
  • a radioactive seed for use in radiation therapy as in claim 1 further including means for blocking the transmission of X-rays comprising a mass of a high atomic number element so placed as to make the seed X-ray visualizable while minimizing the absorption of soft X-rays generated within the seed.
  • a radioactive seed as in claim 13 in which said means for blocking the transmission of X-rays comprises an elongate member having a substantially smaller size than said means disposed within the cavity for maintaining the radioisotope in a substantially uniform distribution, said member being disposed longitudinally and centrally within said cavity.
  • a radioactive seed as in claim 13 in which said means for blocking the transmission of X-rays is a solid ball disposed interiorly of the seed.
  • a method for making a therapeutically radioactive seed comprising soaking a nylon carrier body of an organic polymer in a solution containing the radioactive iodine isotope I so that said body contains a thera eutic amount of the I then placing said body axially inside of a stainless steel tube, and fusing the ends of said tube to seal the same.

Description

3,351,049 IVE ISOTOPE TURE N V- 7. 9 D. c. LAWRENCE THERAPEUTIC METAL SEED CONTAINING WITHIN A RADIOACT DISPOSED ON A CARRIER AND METHOD OF MANUFAC Filed April 12, 1965 Fig.2
INVENTOR.
Q m 2 C mfl O m Y B Fig.4
Attorneys United States Patent This application is a continuation-in-part of my copending application Serial No. 325,332, filed November 21, 1963, now abandoned.
This invention relates to therapeuti radiology. More particularly, it relates to a radioactive X-ray emitting source usually referred to as a seed and a method of manufacture therefor.
Radiation therapy refers to the treatment of diseases especially the treatment of tumors including malignant tumors, such as cancer, with radiation. In radiation therapy, it is desired to destroy the malignant tissue without causing excessive radiation damage to nearby healthy and possibly vital tissues which, because of their proximity, are likely to receive considerable irradiation.
Special methods have been developed for preferentially irradiating deep seated diseased tissue. These include the use of high energy X-ray beams together with cross-fire and rotational techniques by which a radiation pattern is created which has a maximum value localized at the site of the diseased tissue. Even so, some absorption and damage inevitably occurs to the normal tissues through which the radiation beam must pass in order to arrive at such deep seated tissue.
Another method of excellent potential for limiting the region of irradiation utilizes radioactive substances in the form of seeds which are implanted at the region to be irradiated. Radioactive materials which have been used to make such seeds have included radon, radium, and radiogold. Seeds constructed of these materials have been made by methods developed over the last several decades and have been used quite beneficially in therapy. However, the seeds heretofore employed have had several disadvantages which have reduced their use.
The high energy penetrating power of the characteristic radiations of these materials of prior use makes it very diflicult to adequately shield the administering personnel from these emitted radiations. For example, the surgeon who makes the implant of the seed can receive a considerable dosage in his hands or other parts of his body. While under treatment, the patient must be segregated and shielded from others which causes additional expense and inconvenience. Another disadvantage results from the irradiation of the patients healthy tissues outside of the diseased area being treated due to the excessive penetrating power of the radiation produced by the hitherto employed radiation source materials. The characteristic half-lives of some of these prior art materials are rather long, and thus it is necessary that such seeds be removed after the predetermined radiation dosage has been administered to prevent overirradiation and attendant ill efiects. As this usually requires an additional surgical pr cedure, another undesired irradiation of the surgeons hands will occur. When treating inoperable malignancies and especially those which affect vital organs, the removal of such seeds may even be impossible, necessitating, in the case of materials of long half life, separation of the patient from others, including his family, for a long period of time.
Therefore, it is an object of the resent invention to provide an improved therapeutic radioactive source and method of manufacture therefor which will overcome the above named disadvantages.
Another object of the invention is to provide a source and method of manufacture of the above character in which a therapeutic dosage of the desired radioactive material is confined in an encapsulating medium which prevents any migration of leakage from such encapsulation.
Another object of the invention is to provide a improved source and method of manufacture therefor of the above character which will last sufliciently Ion-g to provide a desired amount of radiation and yet not so long as to require removal by surgery after it has performed its function.
Another object of the invention is to provide a source and method of manufacture therefor of the above character in which a therapeutic amount of the appropriate radioactive isotope is encapsulated.
Another object of the invention is to provide a source and method of manufacture therefor of the above character in which the encapsulating medium is nontoxic, corrosion resistant and compatible with biological fluids so that the seed can be left indefinitely in place.
Another object of the invention is to provide a source and method of manufacture therefor of the above character in which the encapsulating medium represents a uniform shadowing effect with respect to the radiations emanated therefrom so that the value of the radiation pattern about the seed is substantially uniform.
Another object of the invention is to provide a source and method of manufacture therefor of the above character in which the radioactive material is uniformly distributed throughout the seed interior so as to prevent localization of the radioactive material and consequent undesirable point source effects.
Another object of the invention is to provide a source and method of manufacture therefor of the above character which can be detected by standard X-ray techniques so that the position of each source can be plotted and the dosage distribution computed.
Another object of the invention is to provide a source and method of manufacture therefor of the above character which retains the substantially uniform radiation pattern thereabout.
Other objects and features of the invention will be ap' parent from the following description and from the accompanying drawings of which:
FIGURE 1 shows a greatly enlarged view of a radioactive source made in accordance with the present invention with portions thereof partially broken away.
FIGURE 2 is a greatly enlarged view of a radioactive source of another embodiment of the invention with the portions thereof partially broken away.
FIGURE 3 is an enlarged view of another embodiment of the invention and showing, in particular, ball means for making the source X-ray detectable.
FIGURE 4 shows a greatly enlarged view of yet another radioactive source made in accordance with the present invention and showing wire means for making the radioactive source X-ray detectable.
This invention is predicated upon the observation that there is a class of radioactive isotopes which characteristically emit a radiation principally limited to low energy X-rays and which have half-lives which are appropriate for obtaining optimum benefits of radiation therapy with seeds while avoiding disadvantages of prior radiation source materials. These isotopes are unique in that their half-lives are sutficiently short that they decay predictably to a negligible output level and therefore can be left permanently and indefinitely implanted within the biological specimen treated. Yet, the radiation energy output intensity and half-lives are sufficiently long to deliver a radiation exposure over an ideal period of time for the optimal therapeutic effect. Thus, the radiation exposure lasts long enough to provide the desired amount of irradiation and yet not so long as to require that the seed be removed by surgery after it has performed its function.
Further, the characteristic radiations of such isotopes are essentially free of alpha and beta emissions, greater than 95% of the radiation being low energy X-rays of energy less than 100 thousand electron volts (hereinafter kev.). Thus, the tissue can be effectively treated while at the same time such radiations can be easily and completely shielded by a relatively thin layer of dense, high-atomic-number material.
The preferred isotopes for use with the invention have radiation characteristics which satisfy the following criteria: a half-life in the range of about 5 to 100 days and preferably about 8 to 80 days. The preferred isotopes are selected with a radiation energy in the soft-X-ray region from about 20 to 100 kev. Preferably, the radiation energy has a value of about 30 kev. Soft X-rays of the above limited energies are easily shielded by thin layers of gold, silver, etc.,"and yet have a reasonable range in soft tissue, the half-value layer being about 2 centimeters. Radioisotopes with half-lives of less than 5 days are generally too short to permit practical processing of the radioisotopes for fabrication and use. Radioisotopes having halflives longer than 100 days emit significant radiation for years and therefore would necessitate removal.
Examples of such suitable isotopes are the monoenergetic X-ray emitting isotopes iodine-125 and cesium- 131. These isotopes have characteristic radiations chiefly consisting of approximately 30 kev. energy X-rays and they also possess half-lives of about 60 and 10 days, respectively. Another isotope example is the isotope palladium-103 having characteristic radiation of about 20 kev. energy and a half-life of about 17 days.
Unfortunately, radioactive iodine has not heretofore been usable for localized treatment of diseased tissue except in the treatment of thyroid tissue, since when iodine is introduced into the body, it tends to concentrate almost entirely in that gland. Consequently, treatment of tissues in other parts of the body with radioactive iodine has not been possible. Similarly, in the case of cesium-131, this isotope has not been used due to the 'fact that it typically distributes uniformly throughout the body and is not long retained in effective concentrations at the location to be treated.
The radioactive seed device of the invention is characterized in that the selected radioisotope is encapsulated in such a manner that it cannot migrate through the encapsulating medium, thereby preventing escape and distribution of the radioisotope throughout the body and possible assimilation and concentration of it in healthy tissues, while, at the same time, permitting the soft X-rays to pass through the capsule wall. Thus, the present invention is able to utilize to advantage the ideal properties of this particular class of radioactive isotopes (i.e. an optimum half-life and characteristic radiation energy) so that advantage can be made of the absorption characteristics of soft X-rays, and that the radiation level is sufiiciently high for a period of time adequate to destroy the diseased tissue and yet the irradiation period is sufficiently short so that the effective exposure terminates predictably decaying away after that tissue is destroyed. Thus, the seed need not be surgically removed from the body but may be left in place indefinitely.
More specifically, there is shown in the accompanying drawing a radioactive seed 10 constructed according to the present invention. The seed 10 comprises a therapeutic amount of a selected X-ray emanating radioisotope 11 appropriately distributed on a carrier body 12 disposed interiorly of a tubular container 13. The container is sealed at its ends 14 and 15 and serves to isolate the radioisotope from physical or chemical interchange between body fluids and the interior of the container while at the same time permitting the radiation to pass through the walls of the container. The selected radioisotope is preferably uniformly distributed along the carrier body 12 to avoid having a point source and to maintain a permanent distribution of the radioactive isotope in a fixed bed throughout the extent of the seed. This configuration assures the optimum dose distribution and the best therapeutic effect. In the case of the palladium-l03 isotope, the distribution of the radioisotope can take the form of a uniform laminar distribution along the carrier body and within the capsule.
As shown in the drawing, the container 13 is preferably designed for implantation as by perforate penetration or injection, e.g., by hypodermic needle or similar device especially designed therefor. As such, the container 13 is preferably constructed in an elongated outside shape, having a relatively narrow outside diameter of from about .5 to 1 millimeter, and about 5 millimeters in length. The interior of the container 13 includes a cavity for receiving the carrier body 12, as hereinafter described. For permanent implantation, as by hypodermic injection, the outside diameter of the seed is constructed about 0.75 millimeter and is thus small enough to pass through a hypodermic needle. For permanent implantation, the seed is constructed approximately 4 mm. long so that it will have a minimal movement in tissue and will not migrate from the area to be treated.
It will be understood that some absorption of the easily attenuated radiation by the wall of the container 13 occurs and that such absorption tends to diminish the amount of radiation useful for irradiating the tissue to be treated. Accordingly, an allowance in the dosage amount is made for such absorption. There is, in any event, a balance between sufficient mechanical strength of the container and the minimum absorption characteristics of the wall which must be obtained for optimum results. I have found that the capsule material should be selected from low-atomic-number materials, preferably of atomic number lying in the range of 4-28. The material must be corrosion resistant, compatible with body tissue and nontoxic, or be provided with a coating possessing these properties. By utilizing low-atomic-number material, absorption is held to a satisfactory low level, consistent with a wall thickness sufficient for structural integrity.
In the embodiment shown in FIGURE 1, the container 13 is constructed of the low atomic numbered metal such as stainless steel alloy or titanium. The stainless steel alloy has been found to have several advantages in that it can be sealed to avoid any migration of contents and it is corrosion resistant, compatible, an nontoxic in use and has a sufficiently low atomic number so that it does not unduly absorb the soft X-rays. The attenuation of stainless steel is about 15% per thousandths of an inch for which additional radioisotope is added to compensate for absorption losses in the container walls. The optimum thickness of stainless steel Wall is in the range of .0005- .003 of an inch. A preferred thickness is about .002 of an inch which represents the best compromise between strength and attenuation losses.
Titanium, having a lower atomic number and higher strength to weight ratio than stainless steel, is exceptionally corrosion resistant and is equally satisfactory from the standpoint of compatibility and nontoxicity in the intended use. Titanium should be selected as a rather pure alloy to assure good working characteristics. The wall thickness of the titanium may vary from .001 of an inch to .005 of an inch, the attenuation being about 5% per thousandths of an inch. An optimum value of wall thickness is approximately .002 of an inch. Titanium has several advantages over stainless steel as a container material. It has high strength to weight ratio, about one-third the attenuation, and it can be sealed by various simple techniques, such as cold compression bonding.
atomic number, such as gold or platinum were used, the
It will be noted that if a metal having a relatively high wall thickness of the container would have to be so small for a source containing a given amount of radioisotope and having the same strength, that the physical strength of the source would be impaired. Otherwise, the amount of radioisotope would have to be increased so much that cost considerations would prevent its use. High atomic numbered materials may be useful, however, as plating over a toxic metal of a low atomic number, without absorbing too great an amount of the radiation. Therefore, to use a low atomic numbered material, such asberyllium, requires that it be supplied with an outer coating of nontoxic, corrosion resistant material such as gold. As to absorption, a container constructed of beryllium can have a wall thickness as high as .035 inch.
The carrier body 12 is provided for collecting, concentrating and supporting the radioisotope and for maintaining it in an appropriately distributed form throughout the container. The carrier body 12 may be formed in a shape generally conforming to that of the interior of the container in which it is to be disposed so that it will not shift in the container. Thus, when disposed in a cylindrical container, the carrier body 12 extends in a cylindrical form substantially throughout the interior thereof and has a diameter approximating that of the inside diameter of the container 13. The carrier body 12 is constructed of any suitable material which will chemically or physically capture the selected radioisotope to thereby maintain a uniform distribution of the isotope in a fixed bed. Such material is preferably selected from the materials composed of elements of low-atomic-number so as to minimize internal absorption of the X-ray radiations.
In the preferred method of preparing the seed of the present invention, the body 12 of selected carrier material is impregnated with the appropriate radioactive isotope at a level suflicient to make up the therapeutic dosage, making allowance for absorption by the encapsulating material. After the carrier body 12 is impregnated, it is placed within the container 11 which is then sealed. The seal of the container must prevent migration of the radioisotope and must not possess undesirable radiation shielding properties which may result from the geometrical configuration of the end. Such undesirable properties causes a shadow effect in the radiation pattern at the region near the ends of the tube.
In accordance with the present invention, the ends 14 and 15 of the container are closed and sealed. For a metallic container 13, this can be accomplished conveniently by closing over the end of the container as by swaging it shut with a swage block having an interior configuration corresponding to the desired exterior configuration at the end of the container. After forming, the end of the container is fused, as by welding, into a uniform shell. By this technique, the container is made into a one-piece unitary structure having a substantially uniform wall thickness. The particular method of formation of the end seal differs somewhat depending upon the par: ticular material chosen for the container. In the case of stainless steel and titanium, the end is mechanically deformed, as by swaging or spinning, to generally close .over the end and then is fused by welding. It is also possible for the ends to be formed by intermetallically joining the walls under pressure or by ultrasonic welding.
Specifically, with respect to stainless steel, ends have been fused by capacitor discharge arc welding. This may tend to thicken the end wall of the container in which case the fused portion is easily trimmed down so that the finished container has a uniform wall thickness throughout.
Titanium metal, which should be selected from a relatively pure alloy having good formability and heat treatability characteristics, is sealed by-spinning the end of the tube down to a point as by turning and spinning by well known techniques. After this, the end may be fused by welding to obtain the end wall of uniform thickness.
Referring now to FIGURE 2, there is shown another embodiment of the invention utilizing a combination of low atomic number materials for the container member. Specifically, the radioactive isotope is distributed uniformly along the length of an elongate carrier body member 21 which is placed inside an aluminum alloy tube 22 (such as that designated by 3003) which is closed over and sealed at its ends 23. The aluminum tubing is sealed in an inert overcoating or container of plastic, ceramic, or precious metal, to prevent reaction of the aluminum with the body fluids over long periods of time. Organic plastic material, such as nylon, silicone rubber, polyester resin, or fluorinated hydrocarbons may be used to form the container 24.
The fluorinated hydrocarbon Teflon FEP has been found to be a very suitable material in that it is exceptionally nonreactive and nontoxic in biological tissues and is available as a heat shrinkable and heat sealable tubing of small diameter. The seed, as shown in FIGURE 2, is very easily manufactured. A short length of aluminum tubing is cut off and sealed at one end. The carrier body 21 containing the active materials is disposed in the aluminum tubing which is then formed to close upon itself at the open and sealed end. The sealed tubing 22 is then placed inside .a plastic tubing which is cut and sealed at its ends by heating. For heat shrinkable plastics, the application of heat, as by an air blast torch, causes not only the ends to seal but the Whole shell to shrink about the tubing 22 to make a very neat, smooth source.
As described, the embodiment as shown in FIGURE 2 is suitable for any of the isotopes contemplated and, in particular, for the isotope iodine-125. The seal provided at the ends of the metal tubing 22 effectively acts to prevent any migration of the iodide out of the capsule.
However, it will be understood that with isotopes such as cesium-131 such seal is not absolutely necessary and the ends of the aluminum tubing may be left open or unsealed. For while a metallic seal is required to prevent migration of 1-125, the plastic seal alone is entirely adequate to contain the Cs131.
The necessary selection of materials of construction of the radioactive seed, according to the present invention, raises a problem which has' not heretofore existed in that the selection requires the use of low-atomic-number materials for surrounding the carrier body. Thus, prior art materials used for other isotopes, such as platinum, iridiurn, gold, and other high atomic number materials are not suitable as an encapsulating medium. In use, it is desirable that the position and number of seeds in the tissue be deter-mined by standard X-ray photographic techniques. That is to say the patient is given an X-ray from which the location of the seeds is plotted. Typically, this information is analyzed by a computer which computes the dose distribution in the tissue being treated. If any cold spots (insufliciently'irradiated areas) are found, they can then be treated by external radiation therapy or other means to greatly improve the chances for destroying the malignancy completely. In the case of the above described X-ray emitting seed, the necessary low atomic number materials of the seeds are not normally visible on an X-ray.
Therefore, there is provided a modified embodiment which incorporates means for blocking the transmission of X-rays to thereby make the seed capable of being detected by X-ray photographic techniques.
Referring specifically to FIGURES 3 and 4, there are shown two embodiments utilizing suchmeans. In FIG- URE 3, there is provided a small ball 26 which is positioned midway in the seed, the carrier body within the seed being formed into portions 27a and b. The ball 26 is constructed of a dense, high-atomic-number material, such as gold, tungsten, etc. The ball 26 is constructed to have a diameter of approximately .002 to .020 of an inch in order to render an image in the X-ray. The carrier bodies 27a and b and ball 26 are housed in a container 28 in the manner heretofore described in connection with the embodiment of FIGURE 1.
Referring specifically to FIGURE 4, there is shown another embodiment utilizing a wire 31 located centrally at the axis of symmetry of the carrier body 32 which is disposed in the low atomic numbered material container 33 in the manner previously described with respect to the embodiment of FIGURE 1. The wire is made of a high atomic number dense material, such as gold, tungsten, etc., and is about .002 to .005 inch in diameter. Tungsten is a particularly suitable material in that its absorption for X-rays of the energy commonly employed to take X-ray photographs is somewhat higher than its absorption of the lower energy X-rays which are emitted by the radioactive isotopes utilized in this invention.
The geometrical disposition of these high atomic numbered materials within the container is especially important in view of their inherent absorption of the low energy X-rays which are provided by the radioisotope in the seed. If large amounts of such high atomic number and dense material were located about the seed, it would severely attenuate radiation therefrom and materially increase the amount of the total radioisotope required for a given strength, making for very inefficient utilization of the radioactivity. As is easily seen in the embodiment of FIGURES 3 and 4, the primary portion of the radiation emanated from the radioisotope can pass out of the seed without encountering these high atomic numbered materials used for rendering the seed X-ray detectable. Furthermore, the location of the high atomic number material should be such as to permit as uniform a radiation pattern as possible from the seed. In this connection, the ball 26 of FIGURE 3 presents some shielding effects about the midsection of the seed, but this shielding appears to be tolerably small.
The following examples are illustrative of the practice of the invention:
IODINE125 A nylon filament 82 mm. long was placed in an aqueous 'bath of 25 millicuries of carrier free I-125. The pH was adjusted to a pH higher than seven by the addition of NaOH, and suflicient NaHSO added to assure that essentially all the iodine-125 was in the iodide oxidation state. The pH was then adjusted to acidic (about pH 3) by the addition of sulfuric acid, sodium nitrite (NaNO was then added to oxidize the iodide to free iodine (I Due to the relative insolubility of free iodine in water and the afiinity of the nylon organic for free iodine, substantially all of the free iodine selectively entered the nylon filament and was removed from the bath. The filament was then taken from the bath and dried and cut into lengths of about 3 /2 mm. The filament lengths were mounted into stainless steel tubular containers. Each container was about 4 mm. long and had an outside diameter of approximately .025 inch and was previously sealed at one end. The containers were then sealed at the other end by being shaped and fused shut in the manner previously described.
CESIUM131 Cesium-131 is separated from the parent barium-131 (which may be produced by neutron irradiation of barium-l30) by selective ion exchange in a column containing [ammonium phosphomolybdate (NH 3 [PMo O (AMP) together with asbestos. Afterwards, the purified cesium- 131 is eluted from the AMP and formed into a bath.
Suitable carrier bodies comprise extruded rods, formed of cellulose acetate binder, acetone and AMP. These rods are used as carrier bodies for absorbing and carrying the predetermined dosage level of cesium-131 available in the bath. The bath is made at least slightly acidic and the rods are placed therein. The preferential affinity of the AMP in the rod absorbs the cesium out of the bath and after which the rods are removed from the bath, dried and sealed with a plastic sealer, such as acrylic plastic, for easier handling. The rods are then encapsulated in suitable containers, such as stainless steel or plastic covered aluminum containers previously described.
PALLADIUM-103 Palladium strongly self-absorbs soft X-rays. To prevent this undesirable circumstance, a thin layer of the radioactive palladium-103 (preferably carrier free) is plated on a plastic rod (nylon) approximately 3 /2 mm. long to a strength of a few millicuries. The rod is then encapsulated in plastic covered (nylon or fluorinated hydrocarbon) aluminum containers as in FIGURE 2. Since the characteristic radiation of the palladium-103 is about 20 kev., an appreciable amount would be absorbed and attenuated by use of material such as stainless steel, rendering the latter economically impractical as an encapsulating material for this radioisotope. For maximum utilization of palladium-103, the effective atomic number of the materials of construction should be as low as practicable (preferably between 4 and 13). For this purpose, an aluminum-plastic capsule is quite suitable.
It is apparent from the foregoing that there has been provided a new and improved radioactive seed and method of manufacture therefor which can be positioned in the region of the body to be treated, and left there indefinitely. After the desired tissue irradiation has been completed, the selected radioactive materials decay away so that the therapy is automatically and gradually cut off without the need for surgical removal of the seed. The container, according to one embodiment, can be detected in X-ray photographs to thereby enable the location and dose distribution to be determined.
While I have disclosed three specific radioactive materials which are especially suited to this application, there are others such as xenon-133 and ytterbium-169 which can be used if proper precautions are taken. The latter isotopes emit only about 50% characteristic X-ray radiations of the desired type, the remainder being essentially higher energy gamma and beta rays which would require additional shielding.
I claim:
1. A radioactive seed for use in radiation therapy of tissue comprising a sealed container having an elongate cavity therein and constructed with walls of substantially uniform thickness, a therapeutic amount of soft X-ray emanating radioisotope disposed within said cavity, said soft X-ray emanating isotope having a characteristic radiation substantially all of which lies between about 20 kev. and kev. and being essentially free from alpha and beta radiations and higher energy X-ray and gamma radiations, said isotope having a half-life from about 8 to 100 days, and means disposed within said cavity for maintaining said radioisotope in a substantially uniform distribution along the length of said cavity, said last named means being made of a material selected to have low absorption for soft X-rays to thereby minimize internal absorption, said container including walls being made of a metal selected to have a relatively low atomic number to thereby minimize the absorption of soft X-rays while completely containing the isotope, said metal being further selected to be nontoxic and nonsoluble in the tissue being treated.
12. A seed for use in radiation therapy of tissue comprising a sealed container having an elongate cavity therein and constructed with walls of substantially uniform thickness, a carrier body means having dimensions for fitting within said cavity and a therapeutic amount of soft X-ray emanating radioisotope uniformly distributed along said carrier body means, said radioisotope being selected from the group consisting of iodine-125, cesium-131, and palladium-103, said carrier body means serving to physically retain the radioisotope in such uniform distribution, said carrier body means being further selected to have a low absorption for soft X-rays to thereby minimize internal absorption, said container being made of a metal having a relatively low atomic number to minimize absorption of soft X-rays while completely containing the isotope, said metal being selected to be nontoxic and nonsoluble in the tissue to be treated.
3. A radioactive seed as in claim 2 in which said isotope is cesium-131 and in which said carrier body means includes ammonium phosphomolybdate for capturing cesium-131.
4. A radioactive seed as in claim 2 in which said radioisotope is palladium-103, and in which the carrier body means is a plastic rod, the palladium-103 being plated on the plastic rod.
5. A radioactive seed as in claim 1 in which the length of the seed is about four mm. and the lateral crosssectional dimension is small enough to permit injection through a hypodermic needle.
6. A seed as in claim 5 in which the lateral crosssectional dimension of said seed is from about .5 to 1.0 millimeters.
7. A seed as in claim 1 in which said metal selected to have a relatively low atomic number is stainless steel having a thickness from about .0005 inch to .003 inch.
8. A seed as in claim 1 in which said metal selected to have a relatively low atomic number is titanium having a thickness from about .001 inch to .005 inch.
9. A seed as in claim 1 in which said container is constructed of an aluminum alloy overcoated with an inert plastic.
10. A radioactive seed for use in radiation therapy comprising a stainless steel tube having its ends fused, and carrier body means formed of an organic polymer containing the radioactive iodine isotope I dispersed therealong, said carrier body being disposed axially within said stainless steel tube.
11. A radioactive seed for use in radiation therapy comprising a stainless steel tube of relatively narrow diameter having its ends fused, a nylon filament containing the radioactive iodine isotope I dispersed therealong, said nylon filament being disposed axially within said stainless steel tube.
12. A radioactive seed in accordance with claim 11 wherein said stainless steel tube has a diameter of less than about of an inch and said nylon filament contains about 5 millicuries of said I per centimeter.
13 A radioactive seed for use in radiation therapy as in claim 1 further including means for blocking the transmission of X-rays comprising a mass of a high atomic number element so placed as to make the seed X-ray visualizable while minimizing the absorption of soft X-rays generated within the seed.
14. A radioactive seed as in claim 13 in which said means for blocking the transmission of X-rays comprises an elongate member having a substantially smaller size than said means disposed within the cavity for maintaining the radioisotope in a substantially uniform distribution, said member being disposed longitudinally and centrally within said cavity.
15. A radioactive seed as in claim 13 in which said means for blocking the transmission of X-rays is a solid ball disposed interiorly of the seed.
16. A method for making a therapeutically radioactive seed comprising soaking a nylon carrier body of an organic polymer in a solution containing the radioactive iodine isotope I so that said body contains a thera eutic amount of the I then placing said body axially inside of a stainless steel tube, and fusing the ends of said tube to seal the same.
References Cited UNITED STATES PATENTS 1,494,826 5/1924 Viol 128-12 2,328,105 12/ 1940 Strobino 252478 2,811,471 10/ 1957 Homeyer. 2,814,296 11/1957 Everett. 3,121,041 2/1964 Stern et a1. 16751 OTHER REFERENCES Silicone Digest, vol. 1, No. 1, October 1959.
C & E News, 39 No. 21; Caged Isotopes May Help Fight Cancer, May 22, 1961, p. 40.
Nuclear Science Abstracts, vol. 16, No. 18, abstract No. 8499, 1962, p. 1091.
Nuclear Science Abstracts, vol. 17, No. 18, abstract No. 30012, 1963, p. 3961.
CARL D. QUARFORTH, Primary Examiner. BENJAMIN R. PADGETT, Examiner. S. J. LECHERT, JR., Assistant Examiner.

Claims (2)

1. A RADIOACTIVE SEED FOR USE IN RADIATION THERAPY OF TISSUE COMPRISING A SEALED CONTAINER HAVING AN ELONGATE CAVITY THEREIN AND CONSTRUCTED WITH WALLS OF SUBSTANTIALLY UNIFORM THICKNESS, A THERAPEUTIC AMOUNT OF SOFT X-RAY EMANATING RADIOISOTOPE DISPOSED WITHIN SAID CAVITY, SAID SOFT X-RAY EMANATING ISOTOPE HAVING A CHARACTERISTIC RADIATION SUBSTANTIALLY ALL OF WHICH LIES BETWEEN ABOUT 20 KEV. AND 100 KEV. AND BEING ESSENTIALLY FREE FROM ALPHA AND BETA RADIATIONS AND HIGHER ENERGY X-RAY AND GAMMA RADIATIONS, SAID ISOTOPE HAVING A HALF-LIFE FROM ABOUT 8 TO 100 DAYS, AND MEANS DISPOSED WITHIN SAID CAVITY FOR MAINTAING SAID RADIOISOTOPE IN A SUBSTANTIALLY UNIFORM DISTRIBUTION ALONG THE LENGTH OF SAID CAVIT, SAID LAST NAMED MEANS BEING MADE OF A MATERIAL SELECTED TO HAVE LOW ABSORPTION FOR SOFT X-RAY TO THEREBY MINIMIZE INTERNAL ABSORPTION, SAID CONTAINER INCLUDING WALLS BEING MADE OF A METAL SELECTED TO HAVE A RELATIVELY LOW ATOMIC NUMBER TO THEREBY MINIMIZE THE ABSORPTION OF SOFT X-RAYS WHILE COMPLETELY CONTAINING THE ISOTOPE, SAID METAL BEING FURTHER SELECTED TO BE NONTOXIC AND NONSOLUBLE IN THE TISSUE BEING TREATED.
16. A METHOD FRO MAKING A THERAPEUTICALLY RADIOACTIVE SEED COMPRISING SOAKING A NYLON CARRIER BODY OF AN ORGANIC POLYMER IS A SOLUTION CONTAINING THE RADIOACTIVE IODINE INSOTOPE I125 SO THAT SAID BODY CONTAINS A THERAPEUTIC AMOUNT OF THE I125 THEN PLACING SAID BODY AXIALLY INSIDE OF A STAINLESS STEEL TUBE, AND FUSING THE ENDS OF SAID TUBE TO SEAL THE SAME.
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